The coupling of capillary electrophoresis (CE) with electrospray-mass spectrometry (ESI-MS) has shown great utility in the analysis of biological matrices. Attributes of CE include low sample and solvent consumption, potentially uncomplicated method development and high efficiency/peak capacity separations. When interfaced with MS, one gains an orthogonal second separation dimension, thus enhancing overall system peak capacity together with the gain of high selectivity and sensitivity via ESI-MS detection. Despite the many advantages of CE-ESI-MS, it has not been widely utilized in the bioanalytical field due to the expertise required to fabricate and operate the interface.
Two interfaces have been developed that enable CE-ESI-MS coupling: the sheath-flow interface and the sheathless interface. Sheath-flow interfaces establish the CE circuit by supplying a flowing conductive ‘sheath’ solution to the capillary outlet enclosed within a stainless steel needle. Application of an appropriate potential to the needle results in the generation of an electrospray from mixing the sheath and the CE effluent. The sheath-flow interface features robust electrospray and easy implementation, but suffers from an inherent loss of analyte sensitivity due to dilution.
To overcome this shortcoming, sheathless interfaces have been developed. When interfacing with ESI-MS, the terminal electrical connection of the CE is held at an ESI potential. Sheathless interfaces have been fabricated that employ electrode insertion or metal deposition at the capillary terminus, a microdialysis junction, a small hand-drilled crack, or hydrofluoric etching to introduce a terminus voltage. While these designs can improve sensitivity relative to sheath-flow interfaces, they can suffer from short capillary lifetimes, dead volume, irreproducible fabrication, fragility, or requiring expertise in handling hydrofluoric acid.
Accordingly, improved devices, systems, and methods for interfacing CE with ESI-MS are needed.